Experimental measures of drug action: agonists
| Term | Suggested Usage | Notes |
|---|---|---|
| EC50 or [A]50 | The molar concentration of an agonist that produces 50% of the maximal possible effect of that agonist. Other percentage values (EC20, EC40, etc.) can be specified. The action of the agonist may be stimulatory or inhibitory. | The mass concentration (g/l) should be used if the molecular weight of the test substance is unknown. |
| It may sometimes be preferable to express the activity of a drug in terms of the concentration that causes a specified change in a baseline measurement (e.g., a 20 mm Hg change in perfusion pressure; a 30% increase in a muscle twitch). If the ECx (or [A]x) terminology is to be used in this context, the appropriate units must be included (e.g., EC20mm or [A]30%) to avoid confusion with EC20 or [A]30 as here defined. | ||
| Because the relation between receptor occupancy and response is usually nonlinear, the EC50 generally does not directly measure the equilibrium dissociation constant of the agonist and therefore is only a descriptive term. | ||
| The term ED50 is sometimes used interchangeably with EC50, but the former term is best reserved for in vivo use where actual doses, as opposed to concentrations, are used. | ||
| ED50 | Either the dose of a drug that produces, on average, a specified all-or-none response in 50% of a test population or, if the response is graded, the dose that produces 50% of the maximal response to that drug. | Units (e.g., mg/kg, mmol/kg or mg/l, mmol/l when a tissue is perfused) to be given. |
| Applicable to in vivo measurements and to those in vitro experiments (e.g., with a perfused tissue) in which absolute concentration is uncertain. Otherwise use EC50. | ||
| In some circumstances, the maximum response will be unknown. This will often be so in clinical pharmacology, for considerations of safety. The effectiveness of a drug may then be best expressed in terms of the dose that causes, for example, a certain change in blood pressure or heart rate. If the ED terminology is to be used for such measurements, the appropriate units must be included (e.g., ED20mm) to avoid confusion with the usage recommended in the left column. | ||
| pEC50 or p[A]50 | The negative logarithm to base 10 of the EC50 of an agonist. | The term pD2 has also been used, particularly in the earlier literature. |
| Maximal agonist effect | The maximal effect that an agonist, whether conventional or inverse, can elicit in a given tissue under particular experimental conditions. It is best expressed as a fraction of the effect produced by a full agonist of the same type acting through the same receptors under the same conditions. | Also referred to historically as intrinsic activity and designated as α. The generic term maximal agonist effect is preferred because maximal effects are highly dependent on the experimental conditions such as tissue used, level of receptor expression, the type of measurement used (e.g., IP3 vs. Ca2+, vs. contraction or secretion), and changes in signal transduction efficiency. Thus intrinsic activity should not be used as a primary pharmacologic characteristic of an agonist as it is not a constant. A simple description of “maximal effect in (specified) assay” is preferred. |
| EMR | Equi-effective molar concentration ratio; the ratio of the molar concentrations of test and reference substances that produce the same biological effect (whether activation or inhibition). | Should be specified only if the log concentration-effect curves for the substances being compared are parallel. |
| EDR | Equi-effective dose ratio, as above, but used when doses rather than concentrations are compared, as in in vivo work. |
EMR, equi-effective molar concentration ratio; EDR, equi-effective dose ratio.